Registration Dossier

Administrative data

Description of key information

The test item is considered to be not sensitizing based on a read-across approach and QSAR predictions with its two components.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There are no experimental data available on the test item. Therefore, the endpoint on skin sensitization is addressed with data on two read-across substances, i. e. the two components of the test item, and QSAR predicitions of these two main components.

Read-across approach

Monoethanolamine (MEA), CAS 141 -43 -5

The sensitizing potential of monoethanolamine (MEA) was studied using the guinea pig maximization test. The animals were induced with MEA and challenged with MEA or tri- or diethanolamine. No statistically significant difference between actively induced animals and control animals was observed and the substance was thus considered to be not sensitizing. There was no indication of cross reactivity, too.

Etidronic acid, CAS 2809 -21 -4

A study on sensitizing potential was conducted with a group of adult female Pirbright White guinea pigs with a mean initial weight of 403 g (test animals) and 402 g (control animals), respectively. The test group consisted of 20 animals; another 20 animals served as controls. The substance was prepared by blending a 5 percent aqueous preparation of the test substance with Freund's adjuvant at a 1 : 1 ratio. Potential skin reactions were read 24 and 48 hours after challenging. Slight positive reactions were obtained from 8 test animals and 5 animals of control 24 hours after challenge and from 5 test animals and 2 animals of control 48 hours after challenge. These reactions were considered to be due to sensitivity of guinea pigs to fat (petrolatum) and not being test substance induced. The body weights of the test and control animals showed a normal and parallel development in the course of the test. The test compound can be graded as no sensitizer for guinea pig.

Justification for Read-Across:

1. HYPOTHESIS FOR THE ANALOGUE APPROACH

The test item is a multi-constituent substance: etidronic acid composed with 2-ethanolamine. Studies on skin sensitization were not performed for the target substance. Reliable experimental data are available for both components, etidronic acid and 2-aminoethanol, which are considered to be suitable read-across substances.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)

2-aminoethanol CAS 141-43-5 is already registered under REACH. The substance purity (analytical grade) for the guinea pig maximization test performed was not specified, however, the impurities diethanolamine (DEA) and triethanolamine (TEA) were found to be present at concentration levels of < 0.1%, respectively. Etidronic acid (Phosphonic acid, P,P'-[1-hydroxyethylidene]bis-, CAS 2809-21-4), the second component, is also registered under REACH. A sensitization study in guinea pigs similar to the method developed by Magnusson and Kligman was performed without documentation of the substance purity. The target substance CAS 42220-47-3 is a composition of etidronic acid and 2-ethanolamine 1:1.

3. ANALOGUE APPROACH JUSTIFICATION

Experimental data, i.e. skin sensitization studies in the guinea pig, are available for 2-aminoethanol and etidronic acid. The GPMT on 2-aminoethanol was performed equivalent to OECD guideline 406. The assay is considered to be reliable and well documented. Skin sensitization study on etidronic acid, performed in 1980, is a pre-GLP and pre-OECD study but still well documented. Both compounds, etidronic acid as well as 2-aminoethanol, are not considered to be sensitizing.

The information given on the two single components is considered to be sufficient to cover the required endpoint information for the composition thereof.

QSAR predictions

 

Both components were assessed by the QSAR tool TIMES for their skin sensitizing potential. Component 2 (CAS 141 -43 -5) was also assessed by QSAR Toolbox. Component 1 (CAS 2809 -21 -4) could not be assessed with QSAR Toolbox, since no analogue structures could be identified by the tool. Taken together, both components of the test item were predicted to be not sensitizing based on QSAR calculations with TIMES, respectively. In addition, component 2 was also predicted to be not sensitizing by QSAR Toolbox. These findings are in line with the experimental data obtained with both components in vivo, respectively, as outlined above.

In conclusion, the test item is not considered to be sensitizing based on available data of its two components (read-across approach) and QSAR predictions thereof.

 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Neither the read-across substances nor QSAR predictions indicated a sensitizing potential for the test item. As a result the substance is not considered to be classified for skin sensitiziation under Regulation (EC) No 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.